EHD3 promotes gastric cancer progression via Wnt/β-catenin/EMT pathway and associates with clinical prognosis and immune infiltration.

Gastric cancer (GC) shows high levels of heterogeneity and predicts a poor prognosis. The expressions of EHD3 are found to be misregulated in a number of tumors. However, the clinical significance and potential function of EHD3 expression in GC patients remain unknown. In this study, we found that EHD3 expression was distinctly increased in GC specimens and cell lines in both TCGA datasets and our cohort. High levels of EHD3 expression were linked to worse outcomes for patients with GC in clinical tests. Nomogram based on multivariate assays displayed good predictive accuracy for GC patients, as evidenced by C-indices and calibration graphs. Low levels of EHD3 mRNA were discovered in GC tissues due to EHD3 methylation's negative regulation of EHD3. In addition, EHD3 was observed to be related to several immune cells and might play a role in successful immunotherapy. Functionally, it was verified that knockdown of EHD3 remarkably suppressed the proliferation, migration and invasion of GC cells in vitro and in vivo. Results of Western blot confirmed that knockdown of EHD3 suppressed the expressions of β-catenin, MMP-9, and N-cadherin, while promoting the expression of E-cadherin. Overall, this research identified a novel GC-related gene EHD3 which might be a novel prognostic biomarker involved in tumor microenvironment. EHD3 promoted the proliferation and metastasis of GC cells through influencing the Wnt/β-catenin/EMT signaling pathway, suggesting it as a novel treatment target for GC patients.